thiosemicarbazide and Breast-Neoplasms

A convenient and selective approach to 13,17-secoestra-1,3,5(10)-trien-17-oic acid [N'-arylcarbothioamido]hydrazides and hybrid molecules containing secosteroid and 1,2,4-triazole fragments was disclosed and these novel types of secosteroids were screened for cytotoxicity against hormone-dependent human breast cancer cell line MCF-7. Most of secosteroid-1,2,4-triazole hybrids showed significant cytotoxic effect comparable or superior to that of the reference drug cisplatin. Hit secosteroid-1,2,4-triazole hybrids 4b and 4h were characterized by high cytotoxicity and good selectivity towards MCF-7 breast cancer cells. PARP cleavage (marker of apoptosis) and ERα and cyclin D1 downregulation were discovered in MCF-7 cells treated with lead secosteroid-1,2,4-triazole hybrid 4b. The synthesized secosteroids may be considered as new promising anticancer agents.

Topics: Antineoplastic Agents; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Drug Screening Assays, Antitumor; Female; Humans; MCF-7 Cells; Molecular Structure; Structure-Activity Relationship; Triazoles

In recent years, researchers were attracted to nanomaterials components for their potential role in cancer treatment. This study aimed to develop a novel and biocompatible cobalt hydroxide (Co(OH)

Topics: Breast Neoplasms; Cobalt; Female; Glutamic Acid; Humans; Hydroxides; Semicarbazides; Spectroscopy, Fourier Transform Infrared; X-Ray Diffraction

The preliminary cytotoxic effect of 4-ethoxycarbonylmethyl-1-(piperidin-4-ylcarbonyl)-thiosemicarbazide hydrochloride (1)-a potent topoisomerase II inhibitor-was measured using a MTT assay. It was found that the compound decreased the number of viable cells in both estrogen receptor-positive MCF-7 and estrogen receptor-negative MDA-MB-231breast cancer cells, with IC(50) values of 146 ± 2 and 132 ± 2 μM, respectively. To clarify the molecular basis of the inhibitory action of 1, molecular docking studies were carried out. The results suggest that 1 targets the ATP binding pocket.

Topics: Adenosine Triphosphate; Breast Neoplasms; Cell Line, Tumor; Cell Survival; DNA Topoisomerases, Type II; Drug Screening Assays, Antitumor; Female; Humans; MCF-7 Cells; Molecular Docking Simulation; Piperidines; Semicarbazides; Topoisomerase II Inhibitors

A series of new organoiridium(III) complexes [Ir(N-C)(2)(N-S)]Cl (HN-C = 2-phenylpyridine (Hppy), N-S = methyl thiosemicarbazide (1), phenyl thiosemicarbazide (2) and naphtyl thiosemicarbazide (3)) have been synthesized and characterized. The crystal structure of (1) has been established by X-ray diffraction, showing the thiosemicarbazide ligand bound to the iridium atom as N,S-chelate. The cytotoxicity studies show that they are more active than cisplatin (about 5-fold) in T47D (breast cancer) at 48 h incubation time. On the other hand, very low resistance factors (RF) of 1-3 in A2780cisR (cisplatin-resistant ovarian carcinoma) at 48 h were observed (RF ≈ 1). Ir accumulation in T47D cell line after 48 h continuous exposure for complexes 1-3 are higher than that corresponding to cisplatin (about 10 times). The complexes 1-3 bind strongly to HSA with binding constants of about 10(4) M(-1) at 296 K, binding occurring at the warfarin site I for 2. Complexes 2 and 3 are also capable of binding in the minor groove of DNA as shown by Hoechst 33258 displacement experiments. Furthermore, complex 2 is also a good cathepsin B inhibitor (an enzyme implicated in a number of cancer related events), being the enzyme reactivated by cysteine.

Topics: Antineoplastic Agents; Binding, Competitive; Breast Neoplasms; Cathepsin B; Cell Line, Tumor; Cell Survival; Crystallography, X-Ray; DNA; Electrophoresis, Gel, Two-Dimensional; Enzyme Activation; Female; Humans; Inhibitory Concentration 50; Iridium; Organometallic Compounds; Ovarian Neoplasms; Semicarbazides; Serum Albumin